A lidocaine cream with improved drug loading concentration and a method for preparing the same

Abstract

This invention discloses a lidocaine cream with increased drug loading concentration and its preparation method, belonging to the field of medical materials technology. This invention utilizes the interaction of nano-sized silk protein with a β-sheet content of not less than 30% with a surfactant to obtain nano-sized encapsulations. Especially when used for lidocaine drug loading, it forms a nano-encapsulated cream with lidocaine, capable of encapsulating active ingredients at concentrations up to 30%. The prepared product has the advantages of room temperature stability, no lidocaine precipitation, and reduced product irritation.

Description

Technical Field

[0001] This invention relates to a cream for increasing lidocaine concentration and preventing lidocaine precipitation, and its preparation method, belonging to the field of medical materials technology. Background Technology

[0002] Lidocaine cream is a commonly used local anesthetic in clinical practice. Existing basic methods and systems aim to achieve high-concentration lidocaine encapsulation through a suitable emulsification system, and utilize the co-solubility of lidocaine with other anesthetic components to prevent crystallization and demulsification at room temperature. Increasing lidocaine concentration can accelerate the onset of action and prolong the duration of anesthetic effect, but it can lead to instability and increased irritation in the emulsion system. Optimizing the design of the emulsification system to achieve a balance between anesthetic efficacy, product stability, and tolerability is the main approach in current product development.

[0003] In the domestic market, only one lidocaine cream from Tongfang Pharmaceutical has obtained approval and registration from the State Food and Drug Administration. This is a strong imitation of the first-generation local anesthetic cream from the American Pliaglis, containing 2.5% lidocaine and 2.5% prilocaine. It utilizes an emulsifier to encapsulate the lidocaine and inhibits recrystallization through the co-solubility of the two anesthetic components. However, in actual use, it suffers from an excessively long onset time and a short duration of action. To address these issues, the second-generation Pliaglis product from the United States optimized the emulsifier system and anesthetic components, developing a cream with 7% lidocaine and 7% prilocaine. This significantly improved both the onset and duration of action, but also significantly increased irritation. Patients commonly experienced side effects such as erythema, edema, and skin discoloration. Furthermore, the product's stability was poor, requiring stringent storage and usage conditions. Koru Pharmaceutical of South Korea also produces lidocaine creams of varying concentrations, but these also failed to resolve the issues of product stability and irritation. Therefore, in order to overcome the existing technological bottlenecks, it is necessary to develop a completely new encapsulation system that is different from traditional emulsifiers, in order to resolve the contradiction between anesthetic effect, product stability and side effects, and bring about a revolutionary breakthrough in the design and development of local anesthetic creams.

[0004] Silk fibroin, as a natural polymer material with excellent properties, has been extensively studied in the biomedical field. Silk fibroin materials are easily shaped, have good biocompatibility, controllable biodegradability, and non-toxic degradation products, making them highly promising for drug carrier preparation. Of course, there has been considerable research on drug loading with silk fibroin: for example, An Tian et al. (Preparation and properties of rifampicin-loaded silk fibroin microspheres [J]. Chinese Journal of Tissue Engineering Research, 2022, 26(10): 1515-1521.) disclosed a rifampicin-loaded silk fibroin microsphere, which used silk fibroin solution as the aqueous phase, liquid paraffin as the oil phase, and Span 80 as the emulsifier to prepare drug-loaded microspheres with a drug loading of 10.56% and an encapsulation rate of 42.78%; and Zhu Zhenghua et al. (Study on the emulsifying properties of silk fibroin solution [J]. Sericultural Science, 2007, 33(2): Patents 250-254 (DOI:10.3969 / j.issn.0257-4799.2007.02.015) indicate that calcium-hydrolyzed silk fibroin solutions possess good emulsifying properties and stability. Specifically, adding an oil to a calcium-hydrolyzed silk fibroin solution and stirring it with a high-speed emulsifier yields an emulsion, laying the material foundation for the preparation of silk fibroin microcapsules. Similarly, patent 201110027281.6 mixes a silk fibroin solution with an oil phase and homogenizes it to obtain an oil-in-water emulsion with an average droplet size of 10-30 μm. All of these indicate that silk fibroin can be used to prepare drug carriers, but the droplet size in the prepared emulsions is all in the micrometer range, and the drug loading efficiency is low. Furthermore, the water dispersibility and stability of the emulsions are difficult to meet the requirements of different pharmaceutical fields.

[0005] Recently, based on an understanding of the silk fibroin assembly process, the inventors utilized the interaction between silk fibroin nanofibers and suitable emulsifiers to prepare nanoscale silk fibroin inclusions under mild conditions. The inclusions, with sizes ranging from 10 to 1000 nm, can be uniformly dispersed in water and exhibit good stability. Considering the structural characteristics of these inclusions, they were further encapsulated with lidocaine. The high stability of the nanofibers inhibited the destruction of the inclusions by lidocaine crystallization at room temperature. This solved the stability problem of high-concentration lidocaine creams without the addition of a co-fluxing agent, and is expected to provide a new solution for the development of novel lidocaine creams. Therefore, this invention is proposed. Summary of the Invention

[0006] To address the aforementioned problems, this invention provides a novel strategy for preparing high-concentration lidocaine cream. The high-concentration lidocaine cream prepared using this method shows no lidocaine precipitation even after prolonged storage at room temperature, demonstrating its excellent stability. This solves the problem of lidocaine precipitation in other existing high-concentration lidocaine creams after long-term storage, and exhibits significant technological advancement.

[0007] The first objective of this invention is to provide a lidocaine cream with increased drug loading concentration, wherein the lidocaine cream comprises nanofibers with a β-sheet content of not less than 30%, a surfactant, lidocaine, and water; the cream system uses nanocapsules with cavities formed by the co-action of nanofibers and surfactants as the dispersion phase, and water as the dispersion medium, wherein the cavities contain lidocaine.

[0008] Furthermore, the lidocaine cream also includes adjuvants such as preservatives and stabilizers, which can be added by those skilled in the art according to actual needs.

[0009] Furthermore, by mass percentage, the content of each component is as follows: 0.2-5% nano-sized silk protein with a β-sheet content of not less than 30%, 0.2-10% surfactant, 1-30% lidocaine, and the balance being water.

[0010] Furthermore, by mass percentage, the contents of each component are as follows: 0.2-5% nano-sized silk protein with a β-sheet content of not less than 30%, 0.2-10% surfactant, 1-30% lidocaine, 0.1-2% auxiliary agent, and the balance being water.

[0011] Furthermore, the surfactant is a nonionic emulsifier.

[0012] Further, the nonionic emulsifier includes polyglycerols, fatty alcohols, fatty acids, glycerol fatty acid esters, sorbitan fatty acid esters, etc. Preferably, it includes polyglycerol-6 distearate, jojoba esters, polyglycerol-3 beeswax ester and cetyl alcohol; polyglycerol-10 laurate; polyglycerol-6 stearate and polyglycerol-6 behenate; polysorbate 20; polyglycerol-3 methyl glucoside distearate; cetearyl alcohol polyether-20; glyceryl stearate citrate; glyceryl stearate; cetyl PEG / PPG-10 / 1 polydimethylsiloxane; stearyl alcohol; capryloyl / decanoyl aminopropyl betaine; cocamidopropyl betaine; sodium cocoamphoacetate; disodium cocoyl glutamate, etc.

[0013] A second objective of this invention is to provide a method for preparing lidocaine cream with increased drug loading concentration, comprising the following steps:

[0014] S1. Prepare nanofibers with a β-sheet content of not less than 30%, mix with water to obtain nanofiber gels or solutions;

[0015] S2. Add lidocaine and surfactant to the nanofiber protein gel or solution to obtain a solid-liquid mixture system;

[0016] S3. Heating the solid-liquid mixture system to melt the substances in the system, thereby obtaining a liquid mixture system;

[0017] S4. Prepare the liquid mixture system into an emulsion to obtain the lidocaine cream.

[0018] This invention first utilizes a process for preparing silk fibroin nanofiber microcapsules. Silk fibroin nanofibers and an emulsifier are thoroughly mixed, followed by the addition of lidocaine powder. The mixture is then heated above the melting point of lidocaine, causing the lidocaine powder to liquefy. Maintaining the temperature above the lidocaine melting point, the mixture undergoes high-speed stirring or homogenization to encapsulate the water-immiscible lidocaine liquid within the silk fibroin nanocapsules. Cooling the lidocaine-encapsulated microcapsule system to room temperature reveals no precipitation of water-insoluble lidocaine powder, confirming complete encapsulation. XRD analysis of the encapsulated components reveals a crystalline state of lidocaine, indicating that the encapsulated lidocaine did not disrupt the silk fibroin encapsulation after reverting from a liquid to a solid crystalline state. Therefore, unlike existing strategies that utilize lidocaine combined with other commensurate components to avoid demulsification due to room-temperature crystallization, this technology leverages the stability of the silk fibroin nanocapsules to maintain the nano-encapsulation state even when lidocaine crystallizes.

[0019] The lidocaine of the present invention forms a stable nanoscale encapsulation through the synergistic effect of nanofiber protein and surfactant, which is more conducive to penetrating the barrier. The encapsulated lidocaine can exist stably in the aqueous environment and remain amorphous at room temperature. Moreover, the encapsulation in the emulsion system carries a large number of active ingredients, which significantly increases the concentration of drug components in the lidocaine system.

[0020] Furthermore, in step S1, the nanofibers of the nanofibers of the nanofibers are 10-1000 nm in diameter.

[0021] Further, in step S1, the nanofiber protein solution is obtained by ultrasonically pulverizing the nanofiber protein gel.

[0022] Furthermore, methods for preparing emulsions from liquid mixtures include, but are not limited to, stirring, high-pressure homogenization, ultrasonic emulsification, and microfluidic emulsification.

[0023] The beneficial effects of this invention are:

[0024] (1) The interaction between nano-sized silk protein with high β-sheet content, surfactant and lidocaine forms a silk protein encapsulating lidocaine nano-encapsulation, which not only has excellent structural stability and high lidocaine encapsulation (up to 30%), but also does not precipitate lidocaine at room temperature under the condition of no other co-soluble components, thus solving the problem of limited lidocaine encapsulation and easy crystallization leading to precipitation in the existing traditional emulsion encapsulation system.

[0025] (2) This invention encapsulates lidocaine with nanofiber protein with excellent biocompatibility, which can effectively reduce the irritation caused by lidocaine and emulsion system in other systems, resolve the contradiction between the anesthetic effect and side effects of high-concentration lidocaine, and provide a better clinical experience.

[0026] (3) The nanofiber protein with high β-sheet content selected in this invention has special hydrophilicity and hydrophobicity, and can avoid lidocaine precipitation at room temperature through non-covalent interaction, so that no other ingredients need to be added, which significantly improves the stability of the cream.

[0027] (4) The lidocaine cream prepared in this invention has a nanoscale encapsulation size, which is more conducive to skin penetration, further shortens the onset time, and improves the anesthetic efficiency.

[0028] (5) The present invention is simple in technology, easy to control, conducive to large-scale preparation, and has high industrialization potential. Attached Figure Description

[0029] Figure 1 Infrared spectrum and atomic force microscopy image of nanofiber silk protein with high β-sheet content;

[0030] Figure 2 Electron micrograph of lidocaine cream;

[0031] Figure 3 X-ray diffraction pattern of lidocaine cream;

[0032] Figure 4 This is a macroscopic diagram of lidocaine cream application. Detailed Implementation

[0033] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention.

[0034] The solutions involved in the embodiments are as follows:

[0035] A lidocaine local anesthetic cream comprising the following components in weight percentages:

[0036] 0.2-5% nanofiber silk protein with high β-sheet content, 0.2-10% surfactant, 1-30% lidocaine, 0.1-2% preservative, balance water;

[0037] Among them, the β-sheet content of nanofiber protein is higher than 30%, and the size is between 10-1000nm, thus having suitable hydrophilicity and hydrophobicity and specific surface area, which can fully interact with lidocaine. The surfactant is a non-ionic surfactant that can remain in liquid state at a suitable temperature to facilitate synergistic action with the silk protein.

[0038] This invention transforms nano-sized silk protein with high β-sheet content, surfactant, and lidocaine into a liquid state at a suitable temperature to facilitate the full interaction of the three components. Subsequently, stirring converts the incompatible components into a proemulsion state. After high-speed stirring or homogenization, the interaction of the nano-sized silk protein, surfactant, and lidocaine forms a silk protein-encapsulated lidocaine nano-encapsulated cream with excellent structural stability and stable dispersion in water. This solves the problem of demulsification and precipitation caused by lidocaine crystallization in existing high-concentration lidocaine creams. The lidocaine is encapsulated within the biocompatible silk protein, effectively preventing direct contact between lidocaine and the skin before transdermal absorption, reducing product irritation, and addressing the problem of existing products easily causing skin discoloration / edema in patients.

[0039] The lidocaine encapsulation in the cream prepared by this invention has a size of 40-200 nm, which is conducive to transdermal absorption and further improves the anesthetic effect. The interaction between nano-sized silk protein and lidocaine directly inhibits lidocaine precipitation, avoids the addition of other co-soluble components, and better improves the controllability and stability of the cream. The technology is simple, easy to control, conducive to large-scale preparation, and has high industrialization potential.

[0040] The preparation method of the above lidocaine cream includes the following steps:

[0041] S1. High β-sheet content nanofiber protein, mixed with water, to obtain high β-sheet content nanofiber protein solution / gel;

[0042] S2. Add surfactant, lidocaine powder, and preservative to the high β-sheet content nanofiber protein solution / gel to obtain a solid-liquid mixture system;

[0043] S3. Heat the mixture until the emulsifier, lidocaine and preservative are completely melted to obtain a liquid mixture.

[0044] S4. Stir and mix the liquid system to allow the emulsifier, lidocaine, and preservative to fully react with the nanofiber protein and mix evenly to form the primary emulsion;

[0045] S5. The colostrum after being mixed evenly is stirred or homogenized at high speed to form nano-encapsulations of lidocaine encapsulated by silk protein, thereby obtaining lidocaine cream.

[0046] In practice, in S1, the appropriate concentration is obtained by combining nano-sized silk protein with water, while in S2, other components are directly added to the complex of silk protein and water to form a solid-liquid mixture system with the expected mass ratio of each component.

[0047] In actual operation, the solid-liquid mixture system mentioned above in S3 is heated to transform the potentially solid emulsifier, preservative and lidocaine powder into liquid, forming a water-oil phase-separated liquid mixture system, so that the different components can interact better; during the heating process, the mixture system can be slowly stirred to promote the temperature balance in the system.

[0048] In actual operation, the mixture in S3 can be heated to 30-100℃ by different heating methods. The surfactant, lidocaine powder and preservative in the mixture are all heated and melted into liquid. The mixture changes from a solid-liquid system to a liquid system with water and oil phase separation.

[0049] In actual operation, in S4, the mixture is heated to transform into a water-oil phase liquid state and then stirred to homogenize it. Under a suitable stirring rate, the silk protein, emulsifier and lidocaine fully interact to form a primary emulsion. The mixture changes from a water-oil phase separation state to a homogeneous primary emulsion state without layering or phase separation.

[0050] Specifically, the stirring speed is 40-300 rpm and the stirring time is 1-120 min.

[0051] In practice, the mixture in the initial emulsion state in S5 is further subjected to high-speed stirring or homogenization. Through the synergistic effect of nanofiber protein, emulsifier and lidocaine, nanofiber encapsulation of lidocaine is formed by silk protein, resulting in a stable lidocaine cream.

[0052] Specifically, the stirring rate of the high-speed stirring treatment in S5 is 1000-4000 rpm, and the stirring time is 1-120 min.

[0053] Specifically, in S5, the homogenization speed is 500-6000 rpm and the homogenization time is 1-120 min.

[0054] Example 1

[0055] This embodiment provides a lidocaine cream comprising the following components in weight percentages: 2% nanofiber silk protein with high β-sheet content, 1% surfactant, 8% lidocaine, 0.5% preservative, and the balance being water.

[0056] The specific steps for preparing the above-mentioned lidocaine cream are as follows:

[0057] (1) High β-sheet content nanofiber protein with a length of 2000 nm and a diameter of 10-30 nm was prepared by concentration-dilution-temperature incubation method, and water was added to mix and the concentration was adjusted to 2% to obtain high β-sheet content nanofiber protein gel.

[0058] (2) Select surfactants with main components of polyglycerol-6 distearate, jojoba esters, polyglycerol-3 beeswax ester, cetyl alcohol, lidocaine powder and pentylene glycol preservative, and add them directly to the silk protein hydrogel in the above proportions to obtain a solid-liquid mixture.

[0059] (3) Under the condition of stirring speed of 40 rpm, the solid-liquid mixture is heated by magnetic heating stirrer to raise the temperature of the mixture to 75°C, so that the surfactant and lidocaine are melted and transformed into a mixture with water-oil phase.

[0060] (4) Stir the water-oil phase mixture at a stirring speed of 150 rpm for 15 minutes to ensure that the different components are fully mixed and homogeneous, so as to obtain a primary emulsion without phase separation or layering.

[0061] (5) Continue stirring the above colostrum at 1000 rpm for 20 minutes to obtain a cream with a lidocaine concentration of 8%.

[0062] (6) When the above cream is cooled to room temperature, no lidocaine is released.

[0063] In this embodiment, the surfactant used is Emulium MelliferaMB manufactured by GAFRAS, France.

[0064] Example 2

[0065] This embodiment provides a lidocaine cream comprising the following components in weight percentages: 3% nanofiber silk protein with high β-sheet content, 2% surfactant, 15% lidocaine, 1% preservative, and the balance being water.

[0066] The specific steps for preparing the above-mentioned lidocaine cream are as follows:

[0067] (1) High β-sheet content nanofibers with a length of 2000 nm and a diameter of 10-30 nm were prepared by concentration-dilution-temperature cultivation method. Water was added and mixed to adjust the concentration to 3%. The nanofibers were in a gel state. The length of the high β-sheet content nanofibers was adjusted by ultrasonic pulverization technology. The ultrasonic power was 100 W and the ultrasonic time was 20 min. The gel was converted into a solution to obtain a high β-sheet content nanofiber solution with a length of 40 nm.

[0068] (2) Polyglycerol-10 laurate surfactant, lidocaine powder and p-hydroxyacetophenone preservative were added directly to the high β-sheet content nanofiber protein solution according to the above mass percentages to obtain a solid-liquid mixture.

[0069] (3) Under the condition of stirring speed of 30 rpm, the solid-liquid mixture is heated by magnetic heating stirrer to raise the temperature of the mixture to 85°C, so that the surfactant, p-hydroxyacetophenone and lidocaine are melted and transformed into a mixture with water-oil phase.

[0070] (4) Stir the water-oil phase mixture at a stirring speed of 250 rpm for 10 minutes to ensure that the different components are fully mixed and homogeneous, so as to obtain a primary emulsion without phase separation or layering.

[0071] (5) The above colostrum was homogenized at 2500 rpm for 3 min to obtain a cream with a lidocaine concentration of 15%.

[0072] (6) When the above cream is cooled to room temperature, no lidocaine is released.

[0073] Example 3

[0074] This embodiment provides a lidocaine cream comprising the following components by weight percentage: 2% nanofiber silk protein with high β-sheet content, 2% surfactant, 30% lidocaine, 0.4% preservative, and the balance being water.

[0075] The specific steps for preparing the above-mentioned lidocaine cream are as follows:

[0076] (1) An amorphous nanofiber protein solution with a length of 200-400 nm and a diameter of 10-20 nm was prepared by dissolving it in a formic acid-lithium bromide mixed solvent. The solution was 1% and incubated at 60 °C for 8 hours to obtain a nanofiber protein gel with high β-sheet content.

[0077] (2) Select polyglycerol-6 distearate surfactant, lidocaine powder and phenoxyethanol preservative, and add them directly to the silk protein gel in the above proportions to obtain a solid-liquid mixture.

[0078] (3) Heat the solid-liquid mixture to raise the temperature of the mixture to 55°C, so that the surfactant and lidocaine melt and transform into a mixture with a water-oil phase.

[0079] (4) Stir the water-oil phase mixture at a stirring speed of 100 rpm for 45 minutes to ensure that the different components are fully mixed and homogeneous, so as to obtain a primary emulsion without phase separation or layering.

[0080] (5) Continue stirring the above colostrum at 1500 rpm for 5 minutes to obtain a cream with a lidocaine concentration of 30%.

[0081] (6) When the above cream is cooled to room temperature, no lidocaine is released.

[0082] Example 4

[0083] This embodiment provides a lidocaine cream comprising the following components in weight percentages: 2% nanofiber silk protein with high β-sheet content, 2% surfactant, 10% lidocaine, 0.5% preservative, and the balance being water.

[0084] The specific steps for preparing the above-mentioned lidocaine cream are as follows:

[0085] (1) High β-sheet content nanofibers with a length of 2000 nm and a diameter of 10-30 nm were prepared by concentration-dilution-temperature cultivation method, and water was added to mix and the concentration was adjusted to 2% to obtain silk protein gel.

[0086] (2) Add the glyceryl stearate surfactant, lidocaine powder and p-hydroxyacetophenone preservative directly to the high β-sheet content nanofiber protein gel according to the above mass percentages to obtain a solid-liquid mixture.

[0087] (3) Under the condition of stirring speed of 30 rpm, the solid-liquid mixture is heated by magnetic heating stirrer to raise the temperature of the mixture to 95°C, so that the surfactant, preservative and lidocaine are melted and transformed into a mixture with water-oil phase.

[0088] (4) Stir the water-oil phase mixture at a stirring speed of 80 rpm for 60 minutes to ensure that the different components are fully mixed and homogeneous, so as to obtain a primary emulsion without phase separation or layering.

[0089] (5) The above colostrum was homogenized at 4500 rpm for 10 min to obtain a cream with a lidocaine concentration of 10%.

[0090] (6) When the above cream is cooled to room temperature, no lidocaine is released.

[0091] Example 5

[0092] The surfactant was replaced with polysorbate 20, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0093] Example 6

[0094] The surfactant was replaced with polyglycerol-3-methylglucose distearate, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0095] Example 7

[0096] The surfactant was replaced with cetearyl alcohol polyether-20, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0097] Example 8

[0098] The surfactant was replaced with glyceryl stearate citrate, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0099] Example 9

[0100] The surfactant was replaced with cetyl PEG / PPG-10 / 1 polydimethylsiloxane, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0101] Example 10

[0102] The surfactant was replaced with capryloyl / decanoyl aminopropyl betaine, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0103] Example 11

[0104] The surfactant was replaced with cocamidopropyl betaine, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0105] Example 12

[0106] The surfactant was replaced with sodium cocoamphoacetate, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0107] Example 13

[0108] The surfactant was replaced with disodium cocoyl glutamate, and the rest was the same as in Example 3. The cream was cooled to room temperature and no lidocaine was precipitated.

[0109] Comparative Example 1

[0110] Without adding surfactants, the rest is the same as in Example 3. The cream is cooled to room temperature, and some lidocaine crystals precipitate out.

[0111] Test case

[0112] 1. Characterization of nanofiber silk fibroin with high β-sheet content

[0113] (1) Infrared spectroscopy test:

[0114] Infrared spectroscopy can effectively characterize the β-sheet structure of silk fibroin. The infrared spectral test results of the nanofiber silk fibroin with high β-sheet content in Example 1 are as follows: Figure 1 As shown in a, nano-sized silk protein is at 1620-1630 cm⁻¹. -1 The presence of a significant absorption peak at 1600-1700 cm⁻¹ indicates that it possesses an abundant β-sheet structure. -1Peak separation was performed on the infrared absorption peak at the point, and the β-sheet content in the silk fibroin was found to be 47%, indicating that the silk fibroin has a stable structure with high β-sheet content and good interaction ability with different hydrophilic and hydrophobic molecules.

[0115] (2) Atomic force microscopy test:

[0116] Atomic force microscopy can be used to detect the nanostructure morphology of nanofiber silk proteins. The atomic force microscopy scanning results of the high β-sheet content nanofiber silk protein in Example 1 are as follows: Figure 1 As shown in b, all the silk proteins used are nanofibers with a diameter of 10-30 nm and a length of 1000-2000 nm.

[0117] 2. Characterization of lidocaine cream

[0118] (1) Scanning electron microscopy test:

[0119] The size of the inclusions is closely related to their stability and transdermal permeability. The microstructure of the prepared inclusions was observed using scanning electron microscopy, such as... Figure 2 As shown, the encapsulation of lidocaine by silk fibroin and surfactant is a nano-encapsulation with a size between 40-200 nm, proving the successful formation of nano-encapsulations.

[0120] (2) XRD results:

[0121] Lidocaine crystallization at room temperature can cause demulsification in traditional emulsification systems, leading to lidocaine precipitation, which is a key factor affecting the instability of cream quality. Other lidocaine creams mainly rely on adding other ingredients to form a eutectic mixture with lidocaine to avoid recrystallization at room temperature, but this method has limitations in terms of dosage and stability. This invention effectively limits lidocaine crystallization and precipitation through silk fibroin nanofiber encapsulation, ensuring cream stability and solving the problem of lidocaine's room temperature stability. Figure 3 As shown, the XRD results of lidocaine cream indicate the presence of XRD peaks for silk fibroin and lidocaine crystallization peaks, suggesting that it crystallizes at room temperature. Figure 2 This indicates that the crystallized stable lidocaine is firmly encapsulated within the silk protein and does not precipitate out, thus forming a state that is stable in both structure and energy, giving the cream excellent stability.

[0122] (3) Macroscopic smearing results:

[0123] The applicability of a cream is a key factor determining its clinical application, such as... Figure 4 As shown in the example, the lidocaine cream prepared in this embodiment can form a uniform coating on the skin surface after application, which is conducive to the uniform local absorption of lidocaine and achieves a good anesthetic effect.

[0124] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A lidocaine cream with improved drug loading concentration, characterized in that: The lidocaine cream comprises nanofiber protein with a β-sheet content of not less than 30%, surfactant, lidocaine and water; the cream system uses nanocapsules with cavities formed by the co-action of nanofiber protein and surfactant as the dispersion phase, and water as the dispersion medium, wherein the cavities contain lidocaine. The method for preparing the lidocaine cream includes the following steps: S1. Prepare nanofibers with a β-sheet content of not less than 30%, mix with water to obtain nanofiber gels or solutions; S2. Add lidocaine and surfactant to the nanofiber protein gel or solution to obtain a solid-liquid mixture system; S3. Heating the solid-liquid mixture system to melt the substances in the system, thereby obtaining a liquid mixture system; S4. Prepare the liquid mixture system into an emulsion to obtain the lidocaine cream; The components, by mass percentage, are: 0.2-5% nano-sized silk protein with a β-sheet content of not less than 30%, 0.2-10% surfactant, 15-30% lidocaine, and the balance being water.

2. The lidocaine cream of claim 1, wherein: The lidocaine cream also includes adjuvants.

3. The lidocaine cream of claim 2, wherein, By mass percentage, the contents of each component are: 0.2-5% nano-sized silk protein with a β-sheet content of not less than 30%, 0.2-10% surfactant, 15-30% lidocaine, 0.1-2% auxiliary agents, and the balance being water.

4. The lidocaine cream of claim 1, wherein: The surfactant is selected from one or more of the following: polyglycerol-6 distearate, jojoba esters, polyglycerol-3 beeswax ester, cetyl alcohol, polyglycerol-10 laurate, polyglycerol-6 stearate, polyglycerol-6 behenate, polysorbate 20, polyglycerol-3 methyl glucoside distearate, cetearyl alcohol polyether-20, glyceryl stearate citrate, glyceryl stearate, cetyl PEG / PPG-10 / 1 polydimethylsiloxane, stearyl alcohol, capryloyl / decanoyl aminopropyl betaine, cocamidopropyl betaine, sodium cocoamphoacetate, and disodium cocoyl glutamate.

5. The lidocaine cream of claim 1, wherein: In step S1, the nanofibers of nanofibers of nanofibers are 10-1000 nm in diameter.

6. The lidocaine cream according to claim 1, characterized in that: In step S3, the temperature is increased to 30-100°C.

7. The lidocaine cream of claim 1, wherein: In step S4, the liquid mixture is first stirred to form a primary emulsion, and then emulsification is performed.

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